crossing96/oncoscreening huggingface dataset:
Fibroblast growth factor receptor 3 activation plays a causative role in urothelial cancer pathogenesis in cooperation with Pten loss in mice.	Although somatic mutations and overexpression of the tyrosine kinase fibroblast growth factor receptor 3 (FGFR3) are strongly associated with bladder cancer, evidence for their functional involvement in the pathogenesis remains elusive. Previously we showed that activation of Fgfr3 alone is not sufficient to initiate urothelial tumourigenesis in mice. Here we hypothesize that cooperating mutations are required for Fgfr3-dependent tumourigenesis in the urothelium and analyse a mouse model in which an inhibitor of Pi3k-Akt signalling, Pten, is deleted in concert with Fgfr3 activation (UroIICreFgfr3(+/) (K644E) Pten(flox) (/flox)). Two main phenotypical characteristics were observed in the urothelium: increased urothelial thickness and abnormal cellular histopathology, including vacuolization, condensed cellular appearance, enlargement of cells and nuclei, and loss of polarity. These changes were not observed when either mutation was present individually. Expression patterns of known urothelial proteins indicated the abnormal cellular differentiation. Furthermore, quantitative analysis showed that Fgfr3 and Pten mutations cooperatively caused cellular enlargement, while Pten contributed to increased cell proliferation. Finally, FGFR3 overexpression was analysed along the level of phosphorylated mTOR in 66 T1 urothelial tumours in tissue microarray, which supported the occurrence of functional association of these two signalling pathways in urothelial pathogenesis. Taken together, this study provides evidence supporting a functional role of FGFR3 in the process of pathogenesis in urothelial neoplasms. Given the wide availability of inhibitors specific to FGF signalling pathways, our model may open the avenue for FGFR3-targeted translation in urothelial disease.	bladder
[Gastric metastases: not only identified at autopsies].	Metastases to the stomach from an extra-digestive neoplasm are an unusual event, identified in less than 2% of cancer patients at autopsy (between 1.7% to 5%). The stomach may be involved by hematogenous spread from a distant primary tumor (most commonly lung, breast and melanoma). Tumors of neighboring organs, such as esophagus, pancreas and gallbladder, may reach the stomach by continuity or by lymphatic-hematogenous spread. Endoscopic routine studies with biopsies have improved the diagnosis of this pathology. Nevertheless, in some cases the histologic study is a false negative because the neoplasia can be placed in the deepest layers of the stomach. We report the case of a 56-year-old man who presented a gastric metastasis of a high gradeuro thelial carcinoma of urinary bladder and we review the literature.	bladder
Association between XPD Lys751Gln polymorphism and bladder cancer susceptibility: an updated and cumulative meta-analysis based on 6,836 cases and 8,251 controls.	The association between xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism and bladder cancer (BC) susceptibility was investigated by two meta-analyses, however, their results were contrary. We conjecture the reason might be the sample size, thus we performed this updated and cumulative meta-analysis using the Comprehensive Meta-Analysis software. We searched PubMed up to August 25th, 2013 and yielded 20 published articles with 21 case-control trails including 6,836 BC patients and 8,251 controls. The meta-analysis results showed that XPD Lys751Gln polymorphism was borderline significantly associated with BC susceptibility for overall population [Gln vs. Lys: OR 1.07, 95% CI 1.01-1.12, P = 0.01; Gln/Gln vs. Lys/Lys: OR 1.15, 95% CI 1.03-1.29, P = 0.01; Gln/Gln vs. (Lys/Gln + Lys/Lys): OR 1.13, 95% CI 1.02-1.26, P = 0.02]. The cumulative meta-analysis according to the publication year showed the CI became increasingly narrower and tended to have statistical significance for the studies incessantly accumulated. In the subgroup analysis according to ethnicity, there was a significant association in Asian population and no association in Caucasian population. There was no publication bias detected. However, due to the limitations and cumulative analysis result of this meta-analysis, more well-designed and larger studies with risk factors adjusted are suggested to be performed to obtain a conclusive result on this topic.	bladder
A novel cellular senescence gene, SENEX, is involved in peripheral regulatory T cells accumulation in aged urinary bladder cancer.	Regulatory T cells (Tregs) play an essential role in sustaining self-tolerance and immune homeostasis. Despite many studies on the correlation between Tregs accumulation and age, or malignancies, the related mechanism hasn't been well explored. To find out the mechanism of Tregs accumulation in aged urinary bladder cancer, we examined the novel cellular senesence gene SENEX and relevant apoptosis gene mRNA expression in sorted CD4+CD25(hi) Tregs from aged UBC donors, evaluated serum cytokine profiles related to tumor immunopathology, and further explored the relationship between SENEX expression, apoptosis gene expression and cytokine secretion. After having silenced down SENEX gene expression with RNA interference, we also evaluated the cellular apoptosis of Tregs sorted from aged UBC patients in response to H₂O₂-mediated stress. Our data indicated that upregulated SENEX mRNA expression in Tregs of aged UBC patients was correlated with pro-apoptotic gene expression and cytokine concentration. Silencing SENEX gene expression increased cellular apoptosis and pro-apoptotic gene expression of Tregs, in response to H₂O₂-mediated stress. Upregulated SENEX mRNA expression together with decreased pro-apoptotic gene expression and disturbances in cytokines synthesis may contribute to the Tregs proliferation and promote tumorigenesis and metastasis. Overall, upregulation of cellular senescence gene SENEX, was associated to regulatory T cells accumulation in aged urinary bladder cancer. Our study provides a new insight into understanding of peripheral Tregs accumulation in aged malignancies.	bladder
Complex association between ERCC2 gene polymorphisms, gender, smoking and the susceptibility to bladder cancer: a meta-analysis.	Genetic polymorphisms in DNA repair genes may be involved in increasing the risk of bladder cancer. Association studies on the excision repair cross-complementation group 2 (ERCC2) gene polymorphisms and bladder cancer risk have reported conflicting results. The aim of this meta-analysis of eligible cancer case-control studies is to investigate the role of ERCC2 SNPs (Arg156Arg, Asp312Asn, and Lys751Gln), gender and smoking in determining susceptibility to bladder cancer. A literature search was conducted in the PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar databases to indentify eligible studies published before December 1, 2013. We performed a meta-analysis of 23 case-control studies with a total of 7,062 bladder cancer patients and 8,832 controls. The overall analysis suggested that ERCC2 Arg156Arg, Asp312Asn, and Lys751Gln are associated with increased bladder cancer risk. For ERCC2 Arg156Arg, the mutant allele was associated with a 1.36-fold (95 % CI=1.15-1.61) increased risk of bladder cancer. For ERCC2 Asp312Asn, individuals with the Asn allele were associated with a 1.29-fold (95 % CI=1.13-1.48) increased risk of bladder cancer. For ERCC2 Lys751Gln, individuals who carried the variant heterozygote Lys/Gln or homozygote Gln/Gln had a significantly increased bladder cancer risk, compared with the wild genotype Lys/Lys (OR=1.10, 95 % CI=1.03-1.18). Furthermore, gender and smoking may modify the association between these SNPs and bladder cancer risk. This study provides the strongest evidence to date for the role of common variants of the ERCC2 gene in bladder carcinogenesis. Further studies comprehensively characterizing other DNA repair pathways and accounting for exposure to relevant environmental factors should offer further insight into the role of DNA repair in bladder cancer.	bladder
[Current developments in the medical treatment of advanced urothelial carcinoma of the bladder].	Medical treatment of advanced urothelial carcinoma of the bladder consists of perioperative treatments as well as palliative chemotherapy in advanced stages. This article focuses on important clinical trials and developments of the last two years, with a review of literature and proceedings of the relevant meetings (ASCO, GU-ASCO, EAU, AUA). The general benefit of perioperative chemotherapy is confirmed. Chemotherapy with Gemcitabin/Cisplatin remains the therapy of choice in the palliative setting. So far, targeted therapies did not show convincing results.	bladder
Fluid intake and risk of bladder cancer in the Nurses' Health Studies.	Increase in fluid intake may reduce bladder cancer risk by decreasing the contact time between carcinogens in urine and bladder epithelium. However, this association has not been examined in a large cohort of women. The association between total fluid intake and bladder cancer risk in two large prospective women's cohorts with 427 incident bladder cancer cases was examined. Detailed information on total fluid intake was collected by repeated food frequency questionnaires over time. Multivariable relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated by using Cox proportional hazards regression models. Results from the two cohorts were pooled together using the random-effects model. Using the average values from the earliest two dietary assessments and lowest quartile as reference, a suggestive inverse association was observed between total fluid intake and overall bladder cancer risk (RR: 0.83, 95% CI: 0.61-1.12, p-value for trend: 0.08), and invasive bladder cancer risk (RR: 0.47, 95% CI: 0.23-0.97, p-value for trend: 0.04). Among heavy cigarette smokers, women with the highest quartile of total fluid intake had a 38% decrease in bladder cancer risk (RR: 0.62, 95% CI: 0.41-0.93, p-value for trend: 0.02). The findings suggested that total fluid intake may reduce bladder cancer risk for female smokers, as well as reduce the risk of invasive bladder cancer.	bladder
Sex disparities in diagnosis of bladder cancer after initial presentation with hematuria: a nationwide claims-based investigation.	BACKGROUND: Women have disproportionately higher mortality rates relative to incidence for bladder cancer. Multiple etiologies have been proposed, including delayed diagnosis and treatment. Guidelines recommend ruling out malignancy in men and women presenting with hematuria. This study sought to determine the difference in timing from presentation with hematuria to diagnosis of bladder cancer in women versus men. METHODS: This is a retrospective population-based study examining the timing from presentation with hematuria to diagnosis of bladder cancer, based on data from the MarketScan databases, which include enrollees of more than 100 health insurance plans of approximately 40 large US employers from 2004 through 2010. All study patients presented with hematuria and were subsequently diagnosed with bladder cancer. The primary outcome measure was number of days between initial presentation with hematuria and diagnosis of bladder cancer by sex. RESULTS: A total of 5416 men and 2233 women met inclusion criteria. Mean days from initial hematuria claim to bladder cancer claim was significantly longer in women (85.4 versus 73.6 days, P < .001), and the proportion of women with >6 month delay in bladder cancer diagnosis was significantly higher (17.3% versus 14.1%, P < .001). Women were more likely to be diagnosed with urinary tract infection (odds ratio = 2.32, 95% confidence interval = 2.07-2.59) and less likely to undergo abdominal or pelvic imaging (odds ratio = 0.80, 95% confidence interval = 0.71-0.89). CONCLUSIONS: Both men and women experience significant delays between presentation with hematuria and diagnosis of bladder cancer, with longer delays for women. This may be partly responsible for the sex-based discrepancy in outcomes associated with bladder cancer.	bladder
Fused lasso algorithm for Cox' proportional hazards and binomial logit models with application to copy number profiles.	This paper presents an efficient algorithm based on the combination of Newton Raphson and Gradient Ascent, for using the fused lasso regression method to construct a genome-based classifier. The characteristic structure of copy number data suggests that feature selection should take genomic location into account for producing more interpretable results for genome-based classifiers. The fused lasso penalty, an extension of the lasso penalty, encourages sparsity of the coefficients and their differences by penalizing the L1-norm for both of them at the same time, thus using genomic location. The major advantage of the algorithm over other existing fused lasso optimization techniques is its ability to predict binomial as well as survival response efficiently. We apply our algorithm to two publicly available datasets in order to predict survival and binary outcomes.	bladder
Methyl jasmonate sensitizes human bladder cancer cells to gambogic acid-induced apoptosis through down-regulation of EZH2 expression by miR-101.	BACKGROUND AND PURPOSE: Gambogic acid (GA) and methyl jasmonate (MJ) are increasingly being recognized as novel natural anticancer compounds. Here, we investigated the antitumour effects of GA in combination with MJ on human bladder cancer cells. EXPERIMENTAL APPROACH: Cell viability was detected by cell counting kit-8 assay. Cell apoptosis was assessed by Hoechst 33258 staining and flow cytometry. Protein levels were determined by immunoblotting and expressions of mRNA and miRNAs by RT-PCR. Differential expressions of a group of downstream genes were identified using microarray analysis. KEY RESULTS: MJ significantly sensitized bladder cancer cells to GA-induced growth inhibition and apoptosis while sparing normal fibroblasts. MJ enhanced GA-induced activation of caspase-3 and caspase-9, and down-regulated the expression of XIAP. Furthermore, treatment of bladder cancer cells with a combination of GA and MJ induced synergistic inhibition of the enhancer of zeste homologue 2 (EZH2) expression, whereas miR-101 expression was up-regulated. Conversely, knockdown of miR-101 restored this decreased expression of EZH2 and suppressed the inhibitory effect of GA and MJ on the growth of bladder cancer cells. Microarray analysis showed that genes closely associated with bladder cancer development were significantly down-regulated by GA and MJ. In a s.c. xenograft mouse model of human bladder carcinoma, the combination of GA and MJ exerted an increased antitumour effect compared with GA alone. CONCLUSION AND IMPLICATIONS: MJ sensitizes bladder cancer cells to GA-induced apoptosis by down-regulating the expression of EZH2 induced by miR-101. Thus, the combination of selective anti-cancer agents MJ and GA could provide a novel strategy for treating human bladder cancer.	bladder
The effect of neoadjuvant chemotherapy on perioperative outcomes in patients who have bladder cancer treated with radical cystectomy: a population-based study.	BACKGROUND: Although therapeutic guidelines recommend the use of neoadjuvant chemotherapy before radical cystectomy (RC) in patients who have muscle-invasive bladder cancer (MIBC), this approach remains largely underused. One of the main reasons for this phenomenon might reside in concerns regarding the risk of morbidity and mortality associated with neoadjuvant chemotherapy. OBJECTIVE: To compare perioperative outcomes between patients receiving neoadjuvant chemotherapy and those treated with RC alone. DESIGN, SETTING, AND PARTICIPANTS: Relying on the Surveillance Epidemiology and End Results-Medicare-linked database, 3760 patients diagnosed with MIBC between 2000 and 2009 were evaluated. INTERVENTION: RC alone or RC plus neoadjuvant chemotherapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Complications occurred within 30 and 90 d after surgery. Heterologous blood transfusions (HBTs), length of stay (LoS), readmission, and perioperative mortality were compared. To decrease the effect of unmeasured confounders associated with treatment selection, propensity score-matched analyses were performed. RESULTS AND LIMITATIONS: Overall, 416 (11.1%) of patients received neoadjuvant chemotherapy. Following propensity score matching, 416 (20%) and 1664 (80%) patients treated with RC plus neoadjuvant chemotherapy and RC alone remained, respectively. The 30-d complication, readmission, and mortality rates were 66.0%, 32.2%, and 5.3%, respectively. The 90-d complication, readmission, and mortality rates were 72.5%, 46.6%, and 8.2%, respectively. When patients were stratified according to neoadjuvant chemotherapy status, no significant differences were observed in the rates of complications, HBT, prolonged LoS, readmission, and mortality between the two groups (all p ≥ 0.1). These results were confirmed in multivariate analyses, where the use of neoadjuvant chemotherapy was not associated with higher risk of 30- and 90-d complications, HBT, prolonged LoS, readmission, and mortality (all p ≥ 0.1). Our study is limited by its retrospective nature. CONCLUSIONS: The use of neoadjuvant chemotherapy is not associated with higher perioperative morbidity or mortality. These results should encourage wider use of neoadjuvant chemotherapy when clinically indicated. PATIENT SUMMARY: Chemotherapy before radical cystectomy in patients with muscle-invasive bladder cancer does not increase the risk of complications or death. The use of chemotherapy should be strongly encouraged, as recommended by clinical guidelines, given its benefits.	bladder
[CCAFU Recommendations 2013: Bladder carcinoma].	INTRODUCTION: The objective was to update the guidelines of the French Urological Association Cancer Committee for non invasive (NMIBC) and invasive bladder cancer (MIBC). METHODS: A Medline search was performed between 2010 and 2013, as regards diagnosis, options of treatment and follow-up of bladder cancer, to evaluate different references with levels of evidence. RESULTS: Diagnosis of NMIBC (Ta, T1, CIS) depends on cystoscopy and complete deep resection of the tumour. The use of fluorescence and a second-look indication are essential to improve initial diagnosis. Risks of both recurrence and progression can be estimated using the EORTC score. A stratification of patients into low, intermediate and high groups is pivotal for recommending adjuvant treatment: instillation of chemotherapy (immediate post-operative, standard schedule) or intravesical BCG (standard schedule and maintenance). Cystectomy is recommended in BCG-refractory patients. Extension evaluation of MIBC is based on pelvic-abdominal and thoracic CT-scan, MRI and FDGPET remain optional. Cystectomy associated with extensive lymph nodes resection is considered the gold standard for non metastatic MIBC. An orthotopic bladder substitution should be proposed to both male and female patients lacking any contraindications and in cases of negative frozen urethral samples, otherwise trans-ileal ureterostomy is recommended as urinary diversion. The interest of neoadjuvant chemotherapy is well known for advanced MIBC as T3-T4 and/or N1-3. As regards metastatic MIBC, first-line chemotherapy using platin is recommended (GC or MVAC), when status (PS<1) and renal function (creatinine clearance > 60 ml/min) permits (only in 50% of cases). In second line treatment, only chemotherapy using vinfluvine has been validated to date. Conclusion.-These new guidelines will hopefully contribute not only to improve patient management, but also diagnosis and treatment for NMIBC and MIBC.	bladder
CD40L gene therapy tilts the myeloid cell profile and promotes infiltration of activated T lymphocytes.	CD40 ligand (CD40L) is a potent stimulator of tumor immunity via its activation of dendritic cells, which in turn initiate T-cell activation. However, T cells are inhibited by suppressive myeloid cells, which constitute an important part of immune evasion. We hypothesized that CD40L may revert the function of suppressive myeloid cells to generate a T-cell stimulatory environment, and this was investigated in the murine bladder cancer model MB49/C57BL/6. Upon intratumoral adenoviral CD40L (AdCD40L) gene therapy, the infiltration of CD11b(+)Gr-1(+) cells was significantly reduced, whereas activated T cells were increased. In vitro, CD40L-expressing MB49 cells tilted the myeloid subpopulations in favor of granulocytic CD11b(+)Gr-1(high) myeloid cells instead of monocytic CD11b(+)Gr-1(int/low) myeloid cells. Further, the level of macrophages in splenocyte co-cultures with MB49 cells was evaluated. In cultures with MB49 cells expressing CD40L, the overall level of macrophages was reduced and the remaining cells were differentiated into M1-like cells. Hence, these data support that CD40L tilts myeloid immune cell populations in favor of anti-tumor immunity (M1) instead of immunosuppression (CD11b(+)Gr-1(int/low) and M2), and this was accompanied by an increased level of activated T cells in the tumor tissue.	bladder
The prognostic value of T1 bladder cancer substaging: a single institution retrospective study.	OBJECTIVE: To evaluate the prognostic value of the depth of lamina propria invasion in patients with T1 bladder cancer. SUBJECTS AND METHODS: 200 patients were treated between the years 2002 and 2009. Tumours with depth of invasion above the muscularis mucosae level were categorised as pT1a and those with depth of invasion up to or beyond the muscularis mucosae as pT1b. RESULTS: Categorisation for pT1a and pT1b was performed in 176 of 200 patients (88%). In 10 patients a muscle-invasive tumour was found in re-transurethral resection samples. 131 (79%) of 166 analysed patients had pT1a tumour and 35 (21%) had pT1b tumour. During the follow-up, in 101 (61%) patients the tumour had recurred and in 27 (16.3%) the tumour had progressed. Of all the investigated parameters, T1 substaging (p < 0.0001), grade (p = 0.0003) and the number of bacillus Calmette-Guérin instillations (p = 0.0490) were significant in predicting progression. The only significant factor for disease-specific survival was T1 substaging in univariable (p = 0.0008) and multivariable (hazard ratio 4.407) analysis. T1 substaging (p = 0.0149) and tumour multiplicity (p = 0.0448) have a statistically significant prognostic value with respect to overall survival. CONCLUSIONS: Deep invasion of the lamina propria is a significant adverse prognostic factor for tumour progression, disease-specific survival and overall survival.	bladder
Paediatric urachal benign teratoma: a case report and review of the literature.	Urachal anomalies are most often seen in children, seldom in adults, but are in general considered rare. The estimated incidence is one in 5000-7000 live births and appears twice as common in males. Despite their rarity, they need to be considered by clinicians, as diseases in the urachus can mimic many abdominal and pelvic conditions and constitute an important differential diagnosis to these. Diagnosis can be made by clinical examination and imaging modalities (computed tomography, ultrasonography, magnetic resonance imaging, voiding cystourethrogram), but some are discovered incidentally. Management of symptomatic urachal anomalies is surgery. Histological examination of the specimen should always be performed to rule out malignancy. We report on the first adolescent described in the literature diagnosed with a urachal sinus harboring a benign teratoma. A combination of the two pathologies is by inference an extremely rare condition, which we here report on and we review the relevant literature on this topic.	bladder